Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
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| 34429967 | Tripterygium wilfordii derivative LLDT-8 targets CD2 in the treatment of rheumatoid arthri | 2021 Oct | Rheumatoid arthritis (RA), a chronic inflammatory synovitis systemic disease, can lead to joint deformities, loss of function and even death. The pathogenesis of RA may be related to genetics, infection and/or sex hormones; however, detailed accounts of the molecular mechanisms underlying its pathogenesis are lacking. In the present study, the synovial tissues of patients with RA and healthy individuals were analyzed to identify the pathogenic signaling pathways and key candidate genes involved in RA. Gene Ontology (GO), pathway enrichment and protein-protein interaction analysis were further used to identify the differentially expressed genes (DEGs) and their potential roles in RA. Molecular docking was used to screen the potential candidate drugs for management of RA. Small interfering RNA was used for knockdown of the CD2 protein. A Cell Counting Kit-8 assay was used to detect the proliferation of cells. Changes in the levels of inflammatory cytokines were detected using ELISA. A total of 279 DEGs were identified in RA; amongst these genes, 166 and 113 were upregulated and downregulated, respectively. GO analysis revealed that the upregulated DEGs were primarily enriched in the activation of the immune and adaptive immune responses, as well as the inflammatory response. The T-cell surface antigen CD2 (CD2) was identified as the most important hub gene by selecting the most important module from the protein-protein interaction network. Knockout of CD2 reduced the damaging effects of TNF-α on synovial cells. Through in situ screening using computer-aided drug design, the triptolide derivative (5R)-5-hydroxytriptolide (LLDT-8) was determined to have the highest docking score based on the CD2 protein structure. Cell experiments showed that LLDT-8 could inhibit the expression of CD2. Cell proliferation and inflammatory cytokine assays confirmed that CD2 was the direct target of LLDT-8. Together, the results of the present study determined factors involved in the pathogenesis of RA and the important role of CD2 in this process by analyzing the DEGs in the RA process. LLDT-8 inhibited CD2 and may thus be used to treat RA. These candidate genes and signaling pathways may serve as potential targets for the clinical treatment of RA. | |
| 34168557 | Prediction and Verification of the Major Ingredients and Molecular Targets of Tripterygii | 2021 | Tripterygii Radix exhibits good clinical efficacy and safety in rheumatoid arthritis (RA) patients, but its effective components and mechanism of action are still unclear. The purpose of this study was to explore and verify the major ingredients and molecular targets of Tripterygii Radix in RA using drug-compounds-biotargets-diseases network and protein-protein interaction (PPI) network analyses. The processes and pathways were derived from Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The most important compounds and biotargets were determined based on the degree values. RA fibroblast-like synoviocytes (RA-FLS) were separated from RA patients and identified by hematoxylin and eosin (HE) staining and immunohistochemistry. The purity of RA-FLS was acquired by flow cytometry marked with CD90 or VCAM-1. RA-FLS were subjected to control, dimethyl sulfoxide (control), kaempferol, or lenalidomide treatment. Cell migration was evaluated by the transwell assay. The relative expression of biotarget proteins and cytokines was analyzed by western blotting and flow cytometry. In total, 144 chemical components were identified from Tripterygii Radix; kaempferol was the most active ingredient among 33 other components. Fourteen proteins were found to be affected in RA from 285 common biotargets. The tumor necrosis factor (TNF) signaling pathway was predicted to be one of the most latent treatment pathways. Migration of RA-FLS was inhibited and the expression of protein kinase B (AKT1), JUN, caspase 3 (CASP3), TNF receptor 1 and 2 (TNFR1 and TNFR2), interleukin-6 (IL-6), and TNF-α was significantly affected by kaempferol. Thus, this study confirmed kaempferol as the effective component of Tripterygii Radix against RA-FLS and TNF signaling pathway and its involvement in the regulation of AKT1, JUN, CASP3, TNFR1, TNFR2, IL-6, and TNF-α expression. | |
| 33841689 | Effect of combined application of iguratimod in the treatment of active rheumatoid arthrit | 2021 | OBJECTIVE: This study was designed to analyse the effect of combined application of iguratimod with methotrexate in the treatment of active rheumatoid arthritis (RA). METHODS: A total of 115 patients with active RA admitted to our hospital were enrolled and divided into group A (n=58) and group B (n=57) according to the method of random number table. Patients in group B were treated with methotrexate alone, while patients in group A were treated with methotrexate combined with iguratimod. The curative efficacy was compared between the two groups. RESULTS: At 6 months after treatment, the levels of CTX-1 and RANKL in group A were higher than those in group B, and the levels of OPG, IL-17 and TGF-α in group A were lower than those in group B (P<0.05). The level of Th17 cells in group A was higher than that in group B, and the level of Treg cells in group A was lower than that in group B at 6 months after treatment (P<0.05). Tender joints count, swollen joints count and DAS28 score in group A were less than those in group B at 6 months after treatment (P<0.05). The duration of morning stiffness of the joints and the score of joint pain degree in group A were less than those in group B at 1, 2, 3, 4, 5, and 6 months after treatment (P<0.05). CONCLUSION: The combined application of methotrexate and iguratimod in the treatment of active RA can effectively improve bone metabolism, regulate the levels of Th17 and Treg cells, play a prominent role in anti-inflammatory effect, and relieve symptoms, and thus achieve a more satisfactory curative effect. | |
| 33815486 | Detection of Genetic Overlap Between Rheumatoid Arthritis and Systemic Lupus Erythematosus | 2021 | BACKGROUND: Clinical and epidemiological studies have suggested systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are comorbidities and common genetic etiologies can partly explain such coexistence. However, shared genetic determinations underlying the two diseases remain largely unknown. METHODS: Our analysis relied on summary statistics available from genome-wide association studies of SLE (N = 23,210) and RA (N = 58,284). We first evaluated the genetic correlation between RA and SLE through the linkage disequilibrium score regression (LDSC). Then, we performed a multiple-tissue eQTL (expression quantitative trait loci) weighted integrative analysis for each of the two diseases and aggregated association evidence across these tissues via the recently proposed harmonic mean P-value (HMP) combination strategy, which can produce a single well-calibrated P-value for correlated test statistics. Afterwards, we conducted the pleiotropy-informed association using conjunction conditional FDR (ccFDR) to identify potential pleiotropic genes associated with both RA and SLE. RESULTS: We found there existed a significant positive genetic correlation (r (g) = 0.404, P = 6.01E-10) via LDSC between RA and SLE. Based on the multiple-tissue eQTL weighted integrative analysis and the HMP combination across various tissues, we discovered 14 potential pleiotropic genes by ccFDR, among which four were likely newly novel genes (i.e., INPP5B, OR5K2, RP11-2C24.5, and CTD-3105H18.4). The SNP effect sizes of these pleiotropic genes were typically positively dependent, with an average correlation of 0.579. Functionally, these genes were implicated in multiple auto-immune relevant pathways such as inositol phosphate metabolic process, membrane and glucagon signaling pathway. CONCLUSION: This study reveals common genetic components between RA and SLE and provides candidate associated loci for understanding of molecular mechanism underlying the comorbidity of the two diseases. | |
| 33732888 | Clinical outcomes and resource utilization analysis in patients with rheumatoid arthritis | 2021 Mar | BACKGROUND AND AIM: The literature is lacking on associations of endoscopic retrograde cholangiopancreatography (ERCP) related outcomes in rheumatoid arthritis (RA) patients. The aim of this study is to evaluate the effects of RA on clinical outcomes and hospital resource utilization in patients undergoing ERCP. METHODS: The National Inpatient Sample database was used to identify hospitalized patients who had underwent an ERCP study from 2012 to 2014 using International Classification of Diseases-Ninth Edition (ICD-9) codes. Primary outcomes were mortality, hospital charges, and length of stay. Secondary outcomes were ERCP-related complications. Chi-squared tests for categorical data and independent t-test for continuous data were utilized. Multivariate analysis was performed to assess the primary outcomes. RESULTS: There was 83 890 ERCP procedures performed, of which 970 patients had RA. In patients with RA, 74.2% were female, and the average age was 65.7 years. RA primary outcomes of mortality rate and hospital cost were lower and statistically significant. There was no statistically significant difference in secondary outcomes except for lower cholecystectomy rates in RA patients. CONCLUSION: With a high inflammatory state, it was hypothesized that RA would be associated with worse outcomes after ERCP. Yet, the primary outcomes of mortality and hospital cost were found to be lower than controls, with no difference in secondary outcomes. We posit that immunosuppressants used to treat RA provides a protective effect to overall complications with ERCP. | |
| 34386699 | Co-Design of a Disease Activity Based Self-Management Approach for Patients with Rheumatoi | 2021 Mar | OBJECTIVE: The systematic development of an intervention to improve disease activity-based management of rheumatoid arthritis (RA) in daily clinical practice that is based on patient-level barriers. METHODS: The self-management strategy was developed through a step-wise approach, in a process of co-design with all stakeholders and by addressing patient level barriers to RA management based on disease activity. RESULTS: The resulting DAS-pass strategy consists of decision supportive information and guidance by a specialised rheumatology nurse. It aims to increase patients' knowledge on DAS28, to empower patients to be involved in disease management, and to improve patients' medication beliefs. The decision supportive information includes an informational leaflet and a patient held record. The nurse individualises the information, stimulates patients to communicate about disease activity, and offers the opportunity for questions or additional support. CONCLUSION: The DAS-pass strategy was found helpful by stakeholders. It can be used to improve RA daily clinical practice. Our systematic approach can be used to improve patient knowledge and self-management on other RA related topics. Also, it can be used to improve the management of other chronic conditions. We therefore provide a detailed description of our methodology to assist those interested in developing an evidence-based strategy for educating and empowering patients. | |
| 34336316 | Fusobacterium nucleatum Pleural Empyema in a Patient with Progressive Rheumatoid Arthritis | 2021 | Fusobacterium nucleatum is an anaerobic oral commensal organism that is often associated with inflammatory bowel disease, adverse pregnancy outcomes, respiratory tract infections, and Lemierre's syndrome. Rheumatoid arthritis is often associated with pleuropulmonary manifestations including noninfectious pleural effusions and interstitial lung disease. We present a case of a 47-year-old man with progressive rheumatoid arthritis on immunosuppressive therapy who was found to have a left-sided pleural effusion, thought secondary to possible pneumonia, and was treated with levofloxacin and methylprednisolone. He presented a month later and was found to have a large left-sided thick-walled fluid collection found to be an empyema. A chest tube was placed, and fluid culture grew Fusobacterium nucleatum. The patient was successfully treated with intrapleural fibrinolytic therapy and amoxicillin-clavulanic acid. | |
| 34178513 | Pancytopenia Resulting From Low-Dose Methotrexate Use: A Diagnostic Challenge. | 2021 May 23 | Rheumatoid arthritis (RA) is a common autoimmune disease primarily affecting small joints which leads to crippling erosion of the articular cartilage and bone. It is associated with complications related to both its disease course and treatment. Methotrexate (MTX) is a folate antagonist responsible for modulating cell-specific signaling pathways and inhibiting the proinflammatory properties of major cell lineages involved in the pathogenesis of RA. It is considered to be the first-line agent in RA because of its disease-modifying ability and safety profile at low doses. This case report discusses how a middle-aged female presented with severe bone marrow suppression secondary to MTX toxicity, an unusual presentation at the usual low-dose regimen. Her presentation overlapped with several other conditions, especially with Felty's syndrome, a rare complication of RA, characterized by the triad of splenomegaly, neutropenia, and RA. Other differentials included hemophagocytic lymphohistiocytosis, hematologic neoplasms, drug reaction, and infection. Therefore, it was essential to exclude all possible differentials before initiating therapy. We found the corrected reticulocyte count coupled with a good response to leucovorin to be an effective way to differentiate MTX-induced pancytopenia from other possible hematologic diagnoses without the use of a bone marrow biopsy. Additionally, our case incidentally demonstrated a potential interaction between piperacillin/tazobactam and MTX. | |
| 34791352 | The Japanese Version of the Patient-Rated Elbow Evaluation is a Useful Outcome Measure tha | 2021 Nov 18 | OBJECTIVE: We examined the relationship between The Japanese version of Patient-Related Elbow Evaluation (PREE-J) and other established subjective and objective outcome measures in Japanese patients with rheumatoid arthritis (RA) who underwent total elbow arthroplasty (TEA). PATIENTS AND METHODS: This study involved 46 elbows of 40 RA patients. We collected clinical data one year after surgery, including the PREE-J, the Mayo Elbow Performance Score (MEPS), Disability of the Arm, Shoulder, and Hand (DASH), and Hand20. The correlation and responsiveness to PREE-J were evaluated compared with other outcome measures pre-and postoperatively. RESULTS: Almost all outcome measures were improved significantly after surgery. Preoperative PREE-J was significantly correlated with preoperative DASH, Hand20, and MEPS. Interestingly, postoperative PREE-J did not correlate with postoperative MEPS. Multiple regression analyses revealed that preoperative grip strength (B = -0.09; 95% CI -0.17 to -0.01, p = 0.03) and preoperative Hand20 (B = 0.31, 95% CI 0.03 - 0.58, p = 0.03) were significant factors those might influenced the postoperative PREE-J. CONCLUSIONS: The PREE-J was shown to correlate well with other preoperative outcome measures among the RA patients included in the current study. The postoperative PREE-J after TEA was influenced by the preoperative grip strength and function of the hand. | |
| 34765383 | Evaluating the Use of Hydroxychloroquine in Treating Patients With Rheumatoid Arthritis. | 2021 Nov | Rheumatoid Arthritis (RA) is one of the most common autoimmune diseases present today. Although treatment options may differ among clinicians, a commonly prescribed treatment is hydroxychloroquine (HCQ), alone or in combination with other medications. HCQ has been studied for its immunomodulatory effects as well as its role in treating adverse conditions associated with RA. This systematic review examined the use of HCQ therapy in RA patients. A systematic search for relevant literature through PubMed, National Institute of Informatics, Japan (CiNii), and Science Direct databases were carried out in August 2021. Literature directly related to HCQ therapy for RA patients, RA-associated chronic kidney disease, and cardiovascular disease (including lipid profile) was considered relevant. HCQ associated retinopathic adverse effects were also selected for this review. Thirty-eight articles were found to be relevant, passed quality assessment, and were included in this review. Nine articles discussed HCQ therapy in comparison with other therapies (mainly methotrexate and sulfasalazine), but were contradictory in their outcomes, as were the seven papers that reviewed kidney function in RA patients with and without HCQ. Five articles credited better cardiovascular outcomes to RA patients taking HCQ. Sixteen articles studied the relationship between HCQ and retinal toxicity, providing insights into the risks associated with HCQ therapy. HCQ therapy was found not only to be beneficial in slowing the disease progression in RA patients but enhanced the effects of methotrexate in treating RA as well. Data strongly associates HCQ therapy with the mitigation of RA-related cardiovascular and kidney conditions. However, if HCQ is prescribed, it is imperative to be aware of the possible (although rare) retinopathic adverse effects associated with this therapy. | |
| 34442739 | Oral Microbiota Identifies Patients in Early Onset Rheumatoid Arthritis. | 2021 Aug 3 | Rheumatoid arthritis (RA) is the most common autoimmune inflammatory disease, and single periodontitis-associated bacteria have been suggested in disease manifestation. Here, the oral microbiota was characterized in relation to the early onset of RA (eRA) taking periodontal status into consideration. 16S rRNA gene amplicon sequencing of saliva bacterial DNA from 61 eRA patients without disease-modifying anti-rheumatic drugs and 59 matched controls was performed. Taxonomic classification at 98.5% was conducted against the Human Oral Microbiome Database, microbiota functions were predicted using PICRUSt, and periodontal status linked from the Swedish quality register for clinically assessed caries and periodontitis. The participants were classified into three distinct microbiota-based cluster groups with cluster allocation differences by eRA status. Independently of periodontal status, eRA patients had enriched levels of Prevotella pleuritidis, Treponema denticola, Porphyromonas endodontalis and Filifactor alocis species and in the Porphyromonas and Fusobacterium genera and functions linked to ornithine metabolism, glucosylceramidase, beta-lactamase resistance, biphenyl degradation, fatty acid metabolism and 17-beta-estradiol-17-dehydrogenase metabolism. The results support a deviating oral microbiota composition already in eRA patients compared with healthy controls and highlight a panel of oral bacteria that may be useful in eRA risk assessment in both periodontally healthy and diseased persons. | |
| 34300218 | Tooth Loss Is Associated with Disease-Related Parameters in Patients with Rheumatoid Arthr | 2021 Jul 9 | BACKGROUND: The aim of this cross-sectional study was to investigate potential associations between periodontal inflamed surface area (PISA) and tooth loss with disease-related parameters in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: Patients who attended the Department of Nephrology and Rheumatology, University Medical Centre Goettingen, Germany, were included. The oral examination comprised the detection of the number of remaining teeth and periodontal condition based on staging and grading matrix. Based on periodontal pockets with positive bleeding on probing, the periodontal inflamed surface area (PISA) was determined. Disease related parameters were extracted from the patients' records. RESULTS: In total, 101 (RA) and 32 participants (AS) were included. Patients with RA had 22.85 ± 4.26 and AS patients 24.34 ± 5.47 remaining teeth (p < 0.01). Periodontitis stage III and IV was present in 91% (RA) and 81.2% (AS) of patients (p = 0.04). Associations between PISA and disease-related parameters were not found in both groups (p > 0.05). In RA, a higher age (p < 0.01), C-reactive protein (p = 0.02), disease activity (p < 0.01) and prednisolone intake (p < 0.01) were associated with fewer remaining teeth. In AS, a higher age (p = 0.02) and increased Bath Ankylosing Spondylitis Metrology Index (p = 0.02) were associated with a lower number of remaining teeth. CONCLUSIONS: Tooth loss is associated with disease activity, especially in RA individuals. Dental care to prevent tooth loss might be recommendable to positively influence oral health condition and disease activity in RA and SA patients. | |
| 34290965 | A double-blind placebo-controlled randomized trial of oral saffron in the treatment of rhe | 2021 Jul | OBJECTIVE: Recently, saffron (Crocus sativus L. from the Iridaceae family) has been characterized by its antioxidant, anti-inflammatory and analgesic effects. This study aimed to evaluate the effect of saffron on disease activity in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: This is a double-blind, placebo-controlled, randomized clinical trial (RCT) performed on 55 newly- diagnosed RA patients without previous treatment, who were randomly divided into intervention (included 28 cases) and control groups (consisted of 27 individuals). Standard therapy including prednisolone, oral methotrexate, folic acid, vitamin D, calcium, and alendronate, was administered similarly in both groups. Patients received a 100 mg saffron pill/day (pure saffron powder) or placebo besides the standard protocol. The placebo had the same shape as the saffron pills. Follow up of DAS28ESR disease activity score was done on the 30th, 45th and 90(th) day of the study. RESULTS: There was no difference between the intervention and control groups regarding to the DAS28ESR at the end of the study. However, a significant decrease in DAS28-ESR was observed in each group compared to the first visit (p=0.001). The results also showed no significant difference in the incidence of side effects in both groups. CONCLUSION: In summary, patients who received pure saffron pills (100 mg/day) in addition to standard therapy did not have a significant difference in improvement of disease activity from the patients on standard therapy. | |
| 34277872 | Rheumatoid Arthritis Susceptibility Is Associated with the KIR2DS4-Full of Killer-Cell Imm | 2021 Apr | BACKGROUND: The pathophysiology underlying the progression and development of autoimmune conditions, such as Rheumatoid Arthritis (RA), is a result of dysregulations of the immune system. Research has explored the genetic alterations present in RA; however, limited studies have examined the role of Killer cell Immunoglobulin-like Receptors (KIR) and Human Leukocyte Antigen (HLA) molecules in RA. Therefore, the aim of this study was to examine KIR genes, their HLA ligands, and KIR-HLA compounds in patients with RA. METHODS: In this case-control study, a total of 50 patients with RA and 100 healthy individuals were enrolled. DNA samples were evaluated using PCR with sequence specific Primers (PCR-SSP). Odds ratio (OR) with a 95% confidence interval (CI) were reported. RESULTS: Among the KIR genes examined, KIR2DLA (p= 0.0255, OR= 0.389, 95% CI= 0.210-0.722) and KIR2DS4-full (p< 0.0001, OR= 6.163, 95% CI= 3.174-11.968) were observed to have a statistically significant correlation with disease susceptibility to RA. As an inhibitory gene, KIR2DLA was observed to have a protective effect against RA while KIR2DS4-full as an activating gene, was found to increase risk for RA. No significant associations were found between any of the other KIR genotypes, HLA ligands, or KIR-HLA compounds examined in this study to RA susceptibility. CONCLUSION: In this study of RA in the Lur population of Iran, KIR2DS4-full was observed to increase susceptibility to RA, while KIR2DL5A was found to act as a protecting factor based on both the cross Table and regression analyses. Further research should focus on repeating this study in additional populations. | |
| 34040897 | Identification of diagnostic genes and vital microRNAs involved in rheumatoid arthritis: b | 2021 | BACKGROUND: The pathogenesis of rheumatoid arthritis (RA) is complex. This study aimed to identify diagnostic biomarkers and transcriptional regulators that underlie RA based on bioinformatics analysis and experimental verification. MATERIAL AND METHODS: We applied weighted gene co-expression network analysis (WGCNA) to analyze dataset GSE55457 and obtained the key module most relevant to the RA phenotype. We then conducted gene function annotation, gene set enrichment analysis (GSEA) and immunocytes quantitative analysis (CIBERSORT). Moreover, the intersection of differentially expressed genes (DEGs) and genes within the key module were entered into the STRING database to construct an interaction network and to mine hub genes. We predicted microRNA (miRNA) using a web-based tool (miRDB). Finally, hub genes and vital miRNAs were validated with independent GEO datasets, RT-qPCR and Western blot. RESULTS: A total of 367 DEGs were characterized by differential expression analysis. The WGCNA method divided genes into 14 modules, and we focused on the turquoise module containing 845 genes. Gene function annotation and GSEA suggested that immune response and inflammatory signaling pathways are the molecular mechanisms behind RA. Nine hub genes were screened from the network and seven vital regulators were obtained using miRNA prediction. CIBERSORT analysis identified five cell types enriched in RA samples, which were closely related to the expression of hub genes. Through ROC curve and RT-qPCR validation, we confirmed five genes that were specific for RA, including CCL25, CXCL9, CXCL10, CXCL11, and CXCL13. Moreover, we selected a representative gene (CXCL10) for Western blot validation. Vital miRNAs verification showed that only the differences in has-miR-573 and has-miR-34a were statistically significant. CONCLUSION: Our study reveals diagnostic genes and vital microRNAs highly related to RA, which could help improve our understanding of the molecular mechanisms underlying the disorder and provide theoretical support for the future exploration of innovative therapeutic approaches. | |
| 34037968 | Comparative Efficacy (DAS28 Remission) of Targeted Immune Modulators for Rheumatoid Arthri | 2021 Jun | INTRODUCTION: The objective of this study was to evaluate the relative efficacy of targeted immune modulators (TIMs) in TIM-naïve/mixed populations (≤ 20% TIM-experienced) and TIM-experienced (> 20% TIM-experienced) adults with moderate-to-severe rheumatoid arthritis with an inadequate response to or intolerance of conventional disease-modifying antirheumatic drugs (cDMARDs). METHODS: A fixed-effects Bayesian network meta-analysis (NMA) was performed using published study-level data from 41 randomized controlled trials (RCTs) identified from two recent systematic literature reviews conducted by the Institute for Clinical and Economic Review, and two additional phase III trials for filgotinib (FINCH-1, FINCH-2). RCTs that compared TIMs with each other, cDMARD therapy, or placebo were included. Treatments included Janus kinase (JAK) inhibitors, tumor necrosis factor α inhibitors (TNFi), and other non-TNFi therapies. Efficacy was defined as achieving remission with a DAS28 score < 2.6 at 12 and 24 weeks. RESULTS: In the 12-week analysis for the TIM-naïve/mixed population, all TIMs combined with cDMARD therapy were significantly more likely to achieve remission compared with a cDMARD alone, with intravenous tocilizumab showing a substantially greater magnitude of effect (odds ratio 19.36; 95% credible interval 11.01-38.16). Similarly, in the 24-week analysis, intravenous and subcutaneous tocilizumab showed the highest odds ratio of achieving DAS28 remission compared with cDMARD therapy. Similar trends were observed for the analyses on monotherapy or TIM-experienced population. CONCLUSIONS: This NMA demonstrated that tocilizumab is associated with a greater likelihood of remission (DAS28 < 2.6) at 12 and 24 weeks compared with most other TIMs, including new JAK inhibitors, when used in combination with a cDMARD or as monotherapy among TIM-naïve/mixed or TIM-experienced populations. | |
| 33910632 | Effect of janus kinase inhibitors and methotrexate combination on malignancy in patients w | 2021 Apr 28 | BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease. The combination therapy of methotrexate (MTX) and Janus kinase inhibitor (JAKi) is commonly used. Patients with RA are at increased risk of malignancy, however, it remains unclear whether the combination therapy is associated with a higher risk. OBJECTIVE: To assess the malignancy risk among patients with RA receiving combination therapy of JAKi and MTX compared to MTX alone. METHODS: PubMed, Cochrane and Embase were thoroughly searched for randomized controlled trials (RCTs) in patients with RA receiving JAKi and MTX, from inception to July 2020. Primary endpoints were malignancy events, Non melanomatous skin cancer (NMSC) and malignancy excluding NMSC and secondary endpoints were serious adverse events (SAE), deaths. Risk ratio (RR) and 95% CI were calculated using the Mantel-Haenszel random-effect method. RESULTS: 659 publications were screened and 13 RCTs with a total of 6911 patients were included in the analysis. There was no statistically significant difference in malignancy [RR = 1.42; 95% CI (0.59, 3.41)], neither NMSC [RR = 1.44 (0.36, 5.76)] nor malignancies excluding NMSC [RR = 1.12 (0.40, 3.13)]. No statistically significant difference between the two groups for SAE [RR = 1.15 (0.90, 1.47)] and deaths [RR = 1.99 (0.75, 5.27)] was found. CONCLUSION: The adjunction of JAKi to MTX is not associated with an increased risk of malignancy when compared to MTX alone. There is no increased risk of SAE and deaths when compared to MTX alone in patients with RA. | |
| 33674957 | Comparison of Efficacy of Ketoprofen and Ibuprofen in Treating Pain in Patients with Rheum | 2021 Jun | INTRODUCTION: Patients with rheumatoid arthritis (RA) or other rheumatic diseases say that pain and stiffness are symptoms affecting their quality of life. Ketoprofen and ibuprofen are the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs) to reduce inflammation and manage mild-to-moderate pain. The aim of this new systematic review of the literature and meta-analysis of randomized controlled trials (RCTs) was to compare the clinical efficacy of ketoprofen and ibuprofen in patients with RA. METHODS: The MEDLINE and EMBASE scientific databases were systematically searched from their inception to November 2020 to identify RCTs directly comparing the recommended therapeutic doses of oral ketoprofen (50-200 mg/day) with ibuprofen (600-1800 mg/day) for RA pain relief. The meta-analysis was made using the standardized mean differences (SMD) of each of the identified RCTs using a fixed effects model. RESULTS: Four RCTs involving 456 patients met the inclusion criteria. The results of the meta-analysis showed a statistically significant difference in efficacy in favor of ketoprofen (0.33, 95% CI 0.14-0.52, p = 0.0005) at all point-estimates of the mean-weighted size effect. The heterogeneity test for the efficacy outcome (the hypothesis was χ(2) = 3.57%, df = 3, p value = 0.31 and the chance of a test effect was 3.49, p = 0.0005) was not significant, and this was confirmed by a Higgins percentage of 16%. The studies included in the meta-analysis did not reveal any significant differences between the two drugs in terms of tolerability or safety. CONCLUSIONS: The result of this meta-analysis shows that ketoprofen is more effective than ibuprofen in managing RA pain at therapeutic doses, thus supporting its use in clinical practice. | |
| 33573047 | The Effect of TNF and Non-TNF-Targeted Biologics on Body Composition in Rheumatoid Arthrit | 2021 Jan 29 | Rheumatoid arthritis (RA) is associated with a decrease in lean mass and stability or even an increase in fat and ectopic adipose tissue. A few data are available on body composition changes under treatment, and data are still controversial. Body composition was assessed before initiation of biologic disease-modifying antirheumatic drug (bDMARD) and after 6 and 12 months of stable treatment. Eighty-three RA patients were included (75% of women, mean age 58.5 ± 10.8 years) of whom 47 patients treated with TNF inhibitor (TNFi), 18 with non-TNF-targeted biologic (Non-TNFi), and 18 with conventional DMARD (cDMARD) alone. In the TNFi group, total lean mass, fat-free mass index, and skeletal muscle mass index significantly increased at 1 year. An increase in subcutaneous adipose tissue (SAT) without change for the visceral or body fat composition was associated. These changes were associated with an improvement in strength and walking test. In non-TNFi or cDMARD groups, no significant changes for body composition or muscle function were observed at 1 year. However, no significant differences for treatment x time interaction were noted between group treatments. In active RA patients starting first bDMARD, treatment with TNFi over 1 year was associated with favorable changes of the body composition and muscle function. | |
| 34135672 | Relationship between different anti-rheumatic drug therapies and complementary and alterna | 2021 May | OBJECTIVES: The use of complementary and alternative medicine (CAM) by patients with rheumatoid arthritis (RA) is highly prevalent. The relationship of these remedies with disease therapy are not fully studied. We aimed to explore the relationship between different anti-rheumatic drug therapy and CAM use in RA patients. METHODS: The study used an interview-based cross-sectional survey in two major referral centres in Riyadh, Saudi Arabia. Patients were adults with confirmed RA that attended rheumatology clinics. Information on the utilization of CAM, RA duration, drug therapy, and laboratory parameters were obtained. Descriptive statistics as well as adjusted odds ratio using bivariate logistic regression were used to explore the different factors related to CAM use, including drug therapy. RESULTS: A total of 438 adult patients with RA were included. The mean (±SD) age of the patients was 49 (±15.0) years. The majority were women 393 (89.7%). Two hundred and ninety-two patients (66.7%) had used CAM. The CAM users who had a longer disease duration (AOR 1.041 [95% CI: 1.011, 1.073]; p = 0.008) were more likely to be female (AOR 2.068 [95% CI: 1.098, 3.896]; p = 0.024), and use methotrexate (AOR 1.918 [95% CI: 1.249, 2.946]; p = 0.003) as opposed to celecoxib (AOR 0.509 [95% CI: 0.307, 0.844]; p = 0.009) and biologic monotherapy (AOR 0.443 [95% CI: 0.224, 0.876]; p = 0.019). Other factors related to CAM were meloxicam use (AOR 2.342 [95% CI: 1.341, 4.089]; p = 0.003) and traditional therapy (AOR 2.989 [95% CI: 1.647, 5.425]; p = 0.000). The remaining factors were not significant. CONCLUSION: CAM use is prevalent in patients with RA. Understanding patients and disease related factors associated with higher use of CAM is warranted to improve RA management and provide more rational use of these remedies. |